This appln is a 371 of PCT/JP99/00931 filed Feb. 26, 1999.
The present invention relates to optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate which is an optically active epoxy compound useful as a raw material for e.g. an optical resolution agent, a high polymer catalyst or a nonlinear material such as a nonlinear optical material, or as a crosslinking agent for a compound or a polymer reactive to an epoxy group, a method for producing it, and a method for producing a high melting point type tris-(2,3-epoxypropyl)-isocyanurate obtained by mixing two enantiomers of the optically active xcex2-type tris- (2,3-epoxypropyl)-isocyanurate thus produced, useful as a high polymer material to be used for the field of electricity and electronic industry materials, or as a crosslinking agent for different compounds or for a reactive high polymer.
To obtain an optically active epoxy compound, a method by asymmetric epoxidation of an olefin has conventionally been known. However, a special and expensive catalyst may be required in this method, or no epoxy compound having a high optical purity tends to be obtained in this method when it is attempted to derive a multifunctional epoxy compound. On the other hand, e.g. an asymmetric resolution method has been known wherein a racemic modification is resolved kinetically by e.g. an enzyme. In this method, it is troublesome to select an enzyme and its conditions, as it is a kinetic resolution method, there is a limit to the optical purity of the compound to be obtained, and no epoxy compound having a high optical purity tends to be obtained when it is attempted to drive a multifunctional epoxy compound, similarly to the above asymmetric epoxidation. From such reasons, no method has been known to produce a multifunctional epoxy compound such as (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate or (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate with a high optical purity. At the same time, no method has been known to optically resolve tris-(2,3-epoxypropyl)-isocyanurate.
Tris-(2,3-epoxypropyl)-isocyanurate has conventionally been known, however, no resolution method nor synthesis method has been known with respect to (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3s)-tris-(2,3-epoxypropyl)-isocyanurate, and accordingly, no example has been reported which discloses these substances themselves which are optically active substances.
A tris-(2,3-epoxypropyl)-isocyanurate has three asymmetric carbon atoms. A racemic mixture of (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate, of which the three asymmetric carbon atoms are coordinate, is commonly called xcex2-type, and is known to provide a crystal having a high melting point of a level of 150xc2x0 C. This is because a pair of these two enantiomers forms a molecular lattice having six strong hydrogen bonds, and this molecular lattice forms a crystal lattice having high-level hydrogen bonds with other molecular lattices.
On the other hand, a mixture of (2R,2R,2S)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2S,2R)-tris-(2,3-epoxypropyl)-isocyanurate, of which only one of the three asymmetric carbon atoms has different optical anisotropy, is commonly called xcex1-type, and provides only a low melting point of a level of 100xc2x0 C. as it does not have a crystal structure as mentioned above.
Since a high melting point type tris-(2,3-epoxypropyl)-isocyanurate not only has a high melting point but has an extremely low solubility in various solvents as compared with e.g. xcex1-type one, when it is used in a form of a one-pack type reactive mixture as a crosslinking agent for different compounds or for a reactive high polymer, the reaction does not proceed during storage until forcible curing under heating. Accordingly, it is used widely in the field of e.g. electricity and electronic industry materials. The method for producing this high melting point type tris-(2,3-epoxypropyl)-isocyanurate is described in e.g. Journal of Thermal Analysis, Vol. 36 (1990) p1819 or Collected papers of High Polymers, Vol. 47, No. 3 (1990) p169, however, there is a drawback such that chlorous impurities derived from decomposed products or epichlorohydrin used as a material are likely to be contained. Further, by the above method, xcex1-type tris-(2,3-epoxypropyl)-isocyanurate as an impurity is likely to be incorporated, and accordingly, it is necessary to make a sacrifice of yield to increase the purity of the high melting point type tris-(2,3-epoxypropyl)-isocyanurate. As the proportion of xcex1-type to xcex2-type as high melting point type, present in the tris-(2,3-epoxypropyl)-isocyanurate obtained by a conventional method, is originally 3:1, the above method is extremely inefficient industrially.
It is to provide (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate, as optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate which is an optically active epoxy compound useful as a high polymer material for e.g. an optical resolution agent or a nonlinear material such as a nonlinear optical material, or as a crosslinking agent for a compound or a high polymer reactive with an epoxy group, a method for efficiently producing it with a high optical purity, and a method for efficiently producing a high melting point type tris-(2,3-epoxypropyl)-isocyanurate with a high purity.
The first aspect of the present invention resides in (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate,
The second aspect of the present invention resides in (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate,
The third aspect of the present invention resides in a method for producing optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate, which comprises reacting isocyanuric acid with an optically active epihalohydrin,
The fourth aspect of the present invention resides in the method for producing optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate according to the above third aspect, which comprises reacting isocyanuric acid with an optically active epihalohydrin by using, as a catalyst, at least one compound selected from the group consisting of a tertiary amine, a quaternary ammonium salt, a tri-substituted phosphine and a quaternary phosphonium salt, to form a 2-hydroxy-3-halopropyl ester of isocyanuric acid, and adding an alkali metal hydroxide or an alkali metal alcoholate to the obtained 2-hydroxy-3-halopropyl ester of isocyanuric acid,
The fifth aspect of the present invention resides in the method for producing optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate according to the above third or fourth aspect, wherein 1 mol of isocyanuric acid and from 3 to 60 mol of the optically active epihalohydrin are reacted,
The sixth aspect of the present invention resides in the method for producing optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate according to any one of the above third to fifth aspects, wherein the water content in the reaction mixed liquid is brought to be less than 1% when 1 mol of isocyanuric acid and the optically active epihalohydrin are reacted,
The seventh aspect of the present invention resides in the method for producing optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate according to any one of the above third to sixth aspects, which comprises, after the formation of the 2-hydroxy-3-halopropyl ester of isocyanuric acid, recovering the optically active epihalohydrin used in an excessive amount by a distillation method, adding a solvent for dilution, and adding an alkali metal hydroxide or an alkali metal alcoholate,
The eighth aspect of the present invention resides in the method for producing optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate according to any one of the above third to seventh aspects, which comprises, after the formation of the 2-hydroxy-3-halopropyl ester of isocyanuric acid, recovering the optically active epihalohydrin used in an excessive amount by a distillation method, adding for dilution a racemic epihalohydrin or an organic solvent which has a solubility of at most 5% in water, in an amount of at least 1 part by weight based on 1 part by weight of the 2-hydroxy-3-halopropyl ester of isocyanuric acid, and adding an alkali metal hydroxide under reflux while removing water,
The ninth aspect of the present invention resides in the method for producing optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate according to any one of the above third to eighth aspects, wherein the optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate is (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate,
The tenth aspect of the present invention resides in the method for producing optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate according to any one of the above third to eighth aspects, wherein the optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate is (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate,
The eleventh aspect of the present invention resides in a method for producing optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate, which comprises optically resolving a racemic modification of tris-(2,3-epoxypropyl)-isocyanurate by using an amylose or cellulose derivative, and
The twelfth aspect of the present invention resides in a method for producing a high melting point type tris-(2,3-epoxypropyl)-isocyanurate with a high purity, which comprises mixing the (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and the (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate which are optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate obtained by the method as defined in the above third to eleventh aspects, with a molar ratio of 1:1.
In the present invention, optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate is (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate.
(2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate has the following structural formula (1): 
Likewise, (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate has the following structural formula (2): 
In the present invention, an optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate may be produced by a method using as materials isocyanuric acid and an optically active epihalohydrin. For example, a method may be mentioned wherein a trialkali metal isocyanurate obtained by reacting isocyanuric acid with an alkali metal hydroxide in an amount three times the isocyanuric acid, and an optically active epihalohydrin, are heated in a solvent, to carry out removal of alkali metal chloride. However, it may be produced preferably by the following method.
Namely, isocyanuric acid and an optically active epihalohydrin are reacted to obtain a 2-hydroxy-3-halopropyl ester of isocyanuric acid, and an alkali metal hydroxide or an alkali metal alcoholate is added thereto.
In the above reaction of isocyanuric acid with an optically active epihalohydrin, the optically active epihalohydrin is added in an amount of from 3 to 60 mol, preferably from 6 to 60 mol, more preferably from 10 to 30 mol, based on 1 mol of isocyanuric acid. Further, as a catalyst, at least one compound selected from the group consisting of a tertiary amine, a quaternary ammonium salt, a tri-substituted phosphine and a quaternary phosphonium salt, is used, and its amount is from 0.001 to 0.1 mol, particularly preferably from 0.01 to 0.05 mol, based on 1 mol is isocyanuric acid.
The reaction of isocyanuric acid with an optically active epihalohydrin is carried out in such conditions that the water content in the entire reaction mixed liquid is less than 1%, preferably at most 0.1%, more preferably at most 100 ppm, and the reaction temperature is from 40 to 115xc2x0 C., preferably from 60 to 100xc2x0 C.
Optically active xcex2-type tris-(2,3-epoxypropyl)-isocyanurate may be produced with a high efficiency, and a side reaction will be suppressed, by adding an alkali metal hydroxide or an alkali metal alcoholate in an amount of preferably from 3.0 to 6.0 mol, more preferably from 3.0 to 4.0 mol, to 1 mol of the 2-hydroxy-3-halopropyl ester of isocyanuric acid as an intermediate.
For the above reaction, in addition to an optically active epihalohydrin, another organic solvent may be used. However, it is preferred to use optically active epichlorohydrin alone as a reaction reagent and as a solvent, since the side reaction which will decompose the desired product will be suppressed, and the reaction rate will be increased.
As epichlorohydrin to be used for industrially producing conventional tris-(2,3-epoxypropyl)-isocyanurate is recovered and recycled as mentioned above, water may be mixed therein. Further, as the reaction of addition of epihalohydrin to isocyanuric acid will be accelerated by adding water to the reaction mixed liquid, the reaction is carried out usually by adding water in an amount of from 1 to 5% based on the entire reaction mixed liquid. However, in the reaction of isocyanuric acid with an optically active epihalohydrin of the present invention, it is preferred to suppress the water content in the entire reaction mixed liquid to be less than 1% so as to suppress the racemization of the optically active epihalohydrin.
As the optically active epihalohydrin, R- or S-epichlorohydrin, epibromohydrin, epiiodohydrin may, for example, be mentioned. Since there is a possibility of racemization when the reaction with isocyanuric acid is carried out at a high temperature, it is preferred to add, as a catalyst to carry out the reaction moderately, at least one compound selected from the group consisting of a tertiary amine, a quaternary ammonium salt, a tri-substituted phosphine and a quaternary phosphonium salt. For example, as the tertiary amine, tripropylamine, tributylamine or N,Nxe2x80x2-dimetylpiperazine may, for example, be mentioned. Further, as the tri-substituted phosphine, tripropylphosphine, tributylphosphine, triphenylphosphine or tritolylphosphine may, for example, be mentioned. Further, as the quaternary ammonium salt, a tetramethylammonium halide, a tetraethylammonium halide or a tetrabutylammonium halide may, for example, be mentioned, and as said halide, chloride, bromide or iodide may, for example, be mentioned. Still further, as the quaternary phosphonium salt, a tetramethylphosphonium halide, a tetrabutylphosphonium halide, a methyltriphenylphosphonium halide or an ethyltriphenylphosphonium halide may, for example, be mentioned, and as said halide, chloride, bromide or iodide may, for example, be mentioned. Among these compounds, preferred are quaternary ammonium salts and quaternary phosphonium salts, as the reaction will proceed efficiently under milder conditions with less side reaction. More preferred are quaternary ammonium salts, and among them, most preferred is a tetraethylammonium halide, and as said halide, it is preferred to use chloride or bromide, since the side reaction will be more suppressed, and the catalyst will be easily removed by washing with water after the reaction.
Further, as the alkali metal hydroxide or the alkali metal alcoholate to be added so as to arouse dehydrohaloganation from the 2-hydroxy-3-halopropyl ester of isocyanuric acid, for example, as the metal hydroxide, sodium hydroxide, potassium hydroxide or lithium hydroxide may be mentioned, and as the alkali metal alcoholate, sodium methylate, sodium ethylate, potassium methylate or potassium ethylate may be mentioned.
If the alkali metal hydroxide or the alkali metal alcoholate is added directly after the formation of the 2-hydroxy-3-halopropyl ester of isocyanuric acid, the optically active epihalohydrin used in an excessive amount tends to undergo racemization. Accordingly, the optically active epihalohydrin used in an excessive amount may be recovered by a distillation method before the addition of the alkali metal hydroxide or the alkali metal alcoholate, followed by adding a solvent for dilution, and then the alkali metal hydroxide or the alkali metal alcoholate may be added. Preferably, the optically active epihalohydrin used in an excessive amount may be recovered by a distillation method, and instead, a racemic epihalohydrin which is industrially easily available at a low cost or an organic solvent having a solubility of at most 5% in water may be added for dilution in an amount of at least 1 part by weight based on 1 part by weight of the 2-hydroxy-3-halopropyl ester of isocyanuric acid, and then the alkali metal hydroxide may be added under reflux while removing water. The solvent to be used is particularly preferably a racemic epihalohydrin since the decomposition of the reaction product will be reduced.
The reaction of treatment with the alkali metal hydroxide is carried out preferably by dropping from 20 to 60 wt %, preferably from 40 to 55 wt %, of an aqueous alkali metal hydroxide solution under reflux while removing water, at a reaction temperature of as low as possible, preferably from 10 to 80xc2x0 C., more preferably from 20 to 70xc2x0 C., and the degree of pressure reduction is adjusted so that the amount of reflux of the racemic epihalohydrin or the organic solvent having a solubility of at most 5% in water will be made large. In the case of dropping from 40 to 55 wt % of an aqueous alkali metal hydroxide solution, the amount of reflux is preferably at least five times the addition amount, since the side reaction to decompose the specified substance tris-(2,3-epoxypropyl)-isocyanurate will be suppressed.
By the above method, (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate can be efficiently produced with a high optical purity. Further, by purification by recrystallization using a solvent such as methanol, it is possible to produce (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate with an optical purity of at least 99% ee.
On the other hand, the present inventors have invented also a method for efficiently producing (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate with a high optical purity, by optical resolution of tris-(2,3-epoxypropyl)-isocyanurate by using an amylose or cellulose derivative.
As the amylose or cellulose derivative to be used in the present invention, a triester derivative or a tricarbamate derivative of amylose or cellulose may be used. Among them, cellulose triphenylcarbamate, cellulose tris-p-tolylcarbamate, cellulose tribenzoate, cellulose triacetate, cellulose tricinnamate, cellulose tris(3,5-dimethylphenylcarbamate), cellulose tris(4-chlorophenylcarbamate), cellulose tris(4-methylbenzoate), amylose tris(3,5-dimethylphenylcarbamate) and amylose tris(1-phenylethylcarbamate) may be mentioned. Among them, particularly preferred is an aromatic type carbamate such as cellulose tris-p-tolylcarbamate, cellulose tris(3,5-dimethylphenylcarbamate), amylose tris(3,5-dimethylphenylcarbamate) or amylose tris(1-phenylethylcarbamate), and the resolution will most efficiently be carried out by amylose tris(3,5-dimethylphenylcarbamate) or amylose tris(1-phenylethylcarbamate).
In the present invention, as the method of optically resolving tris-(2,3-epoxypropyl)-isocyanurate by using the amylose or cellulose derivative, a known method may be used wherein the amylose or cellulose derivative is supported on a silica gel, for example, which is packed in a column, to separate tris-(2,3-epoxypropyl)-isocyanurate by column chromatography. These amylose or cellulose derivative to be used for the optical resolution agent, the column and the like may be used repeatedly, and the optical purity of at least 99% ee and the optical yield of about 100% will be obtained by employing a proper eluent, and accordingly it is an effective production method.
By the above method, (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate can be produced efficiently with a high optical purity. Further, as a result of studies, the present inventors have found that a high melting point type tris-(2,3-epoxypropyl)-isocyanurate can be produced with a high purity in a high yield, by mixing the enantiomers of high purity thus obtained in a molar ratio of 1:1. It may be obtained, for example, by melt-mixing them at a temperature of at least the melting point of both, for example, at 120xc2x0 C.
Further, as another method, (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate are respectively dissolved in a solvent having a high solubility in (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate and having a low solubility in a high melting point type tris-(2,3-epoxypropyl)-isocyanurate, and the respective solutions are mixed to obtain a high melting point type tris-(2,3-epoxypropyl)-isocyanurate with substantially no xcex1-type tris-(2,3-epoxypropyl)-isocyanurate as an impurity contained therein.
As the solvent, a variety of solvents such as halogen type solvents including dichloromethane, chloroform and trichloroethane, aprotic polar solvents including dimethylformamide, dimethylsulfoxide and dimethylacetamide, nitril type solvents including acetonitrile and adiponitrile, ether type solvents including dioxane and tetrahydrofuran, ketone type solvents including acetone and methyl ethyl ketone, as well as ester type solvents including ethyl acetate and aromatic type solvents including benzene and toluene, may, for example, be used. Among them, preferred is a solvent having a solubility of at least 10% at room temperature in (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate. The solvent is preferably liquid in the vicinity of 25xc2x0 C., and has a boiling point of as low as possible, for example, a boiling point of from about 30xc2x0 C. to about 150xc2x0 C., since the solvent will hardly remain as an impurity.
With respect to (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate obtained in the present invention, the compounds themselves may be used as such. Further, they may be cured by using as a curing agent, e.g. a polyvalent active hydrogen compound having reactivity with epoxy, such as an acid anhydride, a polyamine, a polycarboxylic acid, a polyol, a polyphenol or a polymercaptan. In such a case, a Lewis acid such as boron trifluoride or a boron trifluoride complex, a strong acid such as p-toluene sulfonic acid, or a compound to be used commonly as a curing accelerator, such as imidazole, may, for example, be used together, or a Lewis acid such as boron trifluoride or a boron trifluoride complex, imidazole or dicyandiaminde alone may be used as a curing agent for curing. (2R,2xe2x80x2R,2xe2x80x3R)-tris-(2,3-epoxypropyl)-isocyanurate and (2S,2xe2x80x2S,2xe2x80x3S)-tris-(2,3-epoxypropyl)-isocyanurate or cured products thereof, are useful as a stationary phase of an optical resolution agent, as a raw material for high polymer catalysts, or as a nonlinear material such as a nonlinear optical material.
On the other hand, the high melting point type tris-(2,3-epoxypropyl)-isocyanurate also provides a cured product having an excellent heat resistance by the above method, and in addition, it may be used for applications in the field of electricity and electronic industrial materials, as a curing agent for a polyhydric active hydrogen compound having reactivity with epoxy, such as a high polymer having a reactive substituent such as a carboxylic acid. As mentioned above, as the high melting point type tris-(2,3-epoxypropyl)-isocyanurate has a low solubility in a solvent, it has such a characteristic that it can be preserved for a long period of time as a reactive mixed liquid of one-pack type together with a high polymer having a reactive substituent.